Support is requested for the purchase of an Applied Biosystems PROCISE (r) cLC Sequencing System. Applied Biosystems is the only manufacturer of protein sequenators. The PROCISE is a state-of-the-art instrument for automated Edman protein sequencing. The instrument will replace an obsolete Model 477A sequenator that originally was purchased 15 years ago. The PROCISE is approximately 100-fold more sensitive than the 477A, which is currently the sole protein sequenator in a core protein chemistry facility, the Biopolymer Laboratory (BPL), at Brigham and Women's Hospital (BWH). Since 1984, the BPL has provided standard sequencing services to users at BWH, Harvard Medical School and its affiliated teaching hospitals, and other institutions in the US and in foreign countries. In addition, the BPL is a world center for radiosequence analysis, which is done by relatively few laboratories. This technique uses pre.facto radiolabeled protein samples to identify positions of specific amino acids through the periodicity of radioactivity detected in each cycle of the Edman chemistry. This highly sensitive (attomolar) method allows sequence determination of samples not otherwise amenable to sequence analysis or to mass spectrometric characterization. Twelve NIH-funded projects comprise our "major user group." The number of projected sequencing samples, which will keep the new instrument running continuously, and the need for radiosequencing capabilities, make purchase of the PROCISE instrument necessary to achieve the aims of the NIH grants funding the user group. These aims address key questions related to important human diseases, including Alzheimer's disease, Parkinson's disease, multiple sclerosis, and osteoporosis. In addition to providing the means to study these diseases, the improved sensitivity of the PROCISE will open up new opportunities for researchers studying low abundance proteins and who were precluded from applying sequencing methods to their projects due to the relatively low sensitivity of the obsolete 477 instrument. Importantly, as has happened countless times following the introduction of new or improved instrumentation, we fully expect that unforeseen advances in the understanding and treatment of human disease will be enabled by the availability of the PROCISE instrument.